POS0866 THE PARAMETERS RELATED TO DECLINE OF LUNG FUNCTION ON RITUXIMAB THERAPY IN PATIENTS WITH INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SYSTEMIC SCLEROSIS
Authors: L. P. Ananyeva, L. Garzanova, S. Glukhova, O. Desinova, O. Koneva, M. Starovoytova, R. Shayakhmetova, O. Ovsyannikova
Journal: Annals of the Rheumatic Diseases (2022)

Background Rituximab (RTX) is considered as one of the effective options for the treatment of interstitial lung disease associated with systemic sclerosis (ILD-SSc) [1]. Factors that affect the effect of RTX therapy are not well investigated. Objectives To evaluate associations of clinical parameters of the disease with response to RTX therapy in patients with ILD-SSc. Methods This prospective study included 102 patients with ILD- SSc, 86 (84%) of them were women. The mean age was 47.6±12.9 years, mean disease duration 6.2±5.5 years. The mean follow-up period was 12.9±2.1 months. The diffuse cutaneous subset of the disease had 55 pts (54%). 69 (68%) pts were positive for antitopoisomerase-1 antibody (anti-Topo-1). All pts received prednisolone at a dose of 11.3±4.5 mg/day. 49 (68%) subjects were exposed to immunosupressants (IS) at baseline. Subjects were categorized as having improvement if baseline forced vital capacity (FVC % predicted) increased by &gt; 5% [2]. Stabilization was defined as a change in FVC of &lt; 5 % and a decrease of &gt; 5% in FVC as worsened ILD-SSc. Out of the 102 patients who started treatment with RTM, 46 pts (45%, group I) fulfilled the improvement criteria during follow-up. A total of 34 patients (33%) stabilized and 21 (20%,, group 2) worsened during follow-up. We compared patients of groups 1 and 2 and performed the statistical analysis, including the linear regression analysis. Results For the age, baseline diffusing capacity for carbon monoxide (DLCO % of predicted), anti-Topo-1 level, activity index (EScSG-AI) and mean dose of prednisolone there were no differences (all p &gt; 0.05) between the two groups. There was a significant differences between the different response groups in a higher percentage of men (13% in group 1 vs 27% in group 2), patients with a limited form of the disease (40 vs 55%), an initially lower Rodnan skin score (median 10 (4;16) and 6 (4;9) and with ΔmRss of 0 (-1; 2) and 2 (0; 8), р=0,02), lower frequency of anti-Topo-1 (50 vs. 74%) and a higher frequency of prescribing IS before inclusion in the study (68 vs. 38%). Worsened pts initially had a higher FVC (88.8±18.1 vs 74.1±19.8, p=0.01) and DLCO (53.6±19.3 vs. 46.8±17.2, p&gt;0.05), but received the lowest cumulative mean dose of RTX (1.2±0.5 vs 1.9±0.6, p=0.001). The linear regression analysis revealed a number of parameters associated with worsening of FVC (with a sensitivity of 75% and a specificity of 91%). These parameters included a limited subset of the disease (odds ratio (OR) 6.374, 0.83-48.8, p=0.068), increased activity index (OR 2.04, 0.19-4.18, p=0.046) and the presence of arthritis (OR 1.39, 0.08-23.19, p=0.82) at the end of the study. The risk of worsening of FVC was associated with an initially elevated level of creatine phosphokinase (OR 1.02, 0.1-0.84, p=0.054) and a decrease of glomerular filtration rate according to EPI (OR = 1.075,1.0-1.14, p=0.022). In patients initially receiving IS, the OR was 9.85, 1.154-84.066, p=0.033). The highest OR =19.6 (2.4; 156, p=0.005)] was associated with the cumulative mean dose of RTX. Conclusion In this study 45% of the pts improved, one third stabilized, and one fifth worsened over a one-year period. On multivariate analysis, limited scleroderma subsets (dcSSc vs lcSSc), increased activity index, the presence of arthritis at the end of the study, cumulative mean dose of RTX (&lt;2 g per year) were found to be independently associated with the decline of FVC. Identification of this parameters could improve monitoring of rituximab effects References [1]Fernández-Codina A, et.al. Arthritis Rheumatol.2018;70:1820-182 [2]Kafaja S, et.al. Am J Respir Crit Care Med. 2018 Mar 1;197(5):644-652 Disclosure of Interests Lidia P. Ananyeva Speakers bureau: Yes, Consultant of: Yes, Grant/research support from: Yes, Liudmila Garzanova Speakers bureau: Yes, Svetlana Glukhova: None declared, Oxana Desinova Speakers bureau: Yes, Consultant of: Yes, Olga Koneva Speakers bureau: Yes, Consultant of: Yes, Grant/research support from: Yes, Mayya Starovoytova Speakers bureau: Yes, Paid instructor for: Yes, Consultant of: Yes, Rushana Shayakhmetova: None declared, Olga Ovsyannikova: None declared